1. Field of the Invention
The present invention relates to a human cell line useful for the preparation of monoclonal antibody-secreting human-human hybridomas.
2. Description of the Prior Art
The preparation of hybridoma cell lines derived by fusing a mouse myeloma cell line and mouse B-lymphocytes sensitized against a given antigen is by now well known in the art. For example, based on the original work by Kohler, G. and Milstein, C. (Nature 256: 495-497 (1975); European Journal of Immunology, Vol. 6, pp. 511-519 (1976), see also Milstein, C.: "Monoclonal Antibodies", Scientific American, Vol. 243: 66-74 (1980)), Koprowski et al, in U.S. Pat. No. 4,172,124, prepared somatic cell hybrids between hypoxanthine phosphoribosyl transferase (HPRT) deficient (HPRT.sup.-) cells and spleen or lymph cells derived from a mouse previously primed with tumor cells. Koprowski et al, in U.S. Pat. No. 4,196,265, prepared continuous cell lines of genetically stable fused cell hybrids capable of producing large amounts of monoclonal antibodies against specific viruses and their antigenic determinants. The cell lines of Koprowski et al '265 are fused cell hybrids between viral antibody producing cells and myeloma cells. Wands et al, U.S. Pat. No. 4,271,145, disclose cell lines for producing monoclonal antibodies to hepatitis virus established by immunizing animal lymphocytes with hepatitis antigen to form antibody- producing cells which are then fused with myeloma cells.
The aforementioned prior art references, however, disclose only hybridomas derived from non-human (in most cases mouse) myeloma and non-human lymphocyte cells.
It has been recognized (see for example Milstein, C., Scientific American supra, at 74) that for a variety of therapeutic applications, antibodies derived from human lymphocytes rather than from the mouse or the rat would be much more desirable. Although chimeric hybridomas have been obtained by fusing mouse myeloma cells with human IgG-producing cells (Levy, R. and Dilley, J., Proceedings of the National Academy of Sciences U.S.A., 75:2411-2415 (1978)), these hybrids tend to be unstable due to the fact that when human cells are fused with non-human cells there is a rapid preferential loss of human chromosomes from the resulting interspecific hybrid cells.
In fact, in October, 1980, Milstein (Scientific American, supra) stated that "so far, the search for a suitable human myeloma line that can be cultured and fused to make an intraspecific hybrid has not borne fruit".
There exists a need therefore for a successful method for preparing human-human hybridoma cell lines. This need would be fulfilled with the existence of an appropriate, long surviving, pure, continuous human cell line capable of being fused with human B-lymphocytes to produce said hybridoma lines.